TY - JOUR
T1 - Drugging the undruggable
T2 - Transcription therapy for cancer
AU - Yan, Chunhong
AU - Higgins, Paul J.
N1 - Funding Information:
This work was supported by NIH grants R01CA164006 and R01CA139107 to CY and R01GM057242 to PJH.
PY - 2013/1
Y1 - 2013/1
N2 - Transcriptional regulation is often the convergence point of oncogenic signaling. It is not surprising, therefore, that aberrant gene expression is a hallmark of cancer. Transformed cells often develop a dependency on such a reprogramming highlighting the therapeutic potential of rectifying cancer-associated transcriptional abnormalities in malignant cells. Although transcription is traditionally considered as undruggable, agents have been developed that target various levels of transcriptional regulation including DNA binding by transcription factors, protein-protein interactions, and epigenetic alterations. Some of these agents have been approved for clinical use or entered clinical trials. While artificial transcription factors have been developed that can theoretically modulate expression of any given gene, the emergence of reliable reporter assays greatly facilitates the search for transcription-targeted agents. This review provides a comprehensive overview of these developments, and discusses various strategies applicable for developing transcription-targeted therapeutic agents.
AB - Transcriptional regulation is often the convergence point of oncogenic signaling. It is not surprising, therefore, that aberrant gene expression is a hallmark of cancer. Transformed cells often develop a dependency on such a reprogramming highlighting the therapeutic potential of rectifying cancer-associated transcriptional abnormalities in malignant cells. Although transcription is traditionally considered as undruggable, agents have been developed that target various levels of transcriptional regulation including DNA binding by transcription factors, protein-protein interactions, and epigenetic alterations. Some of these agents have been approved for clinical use or entered clinical trials. While artificial transcription factors have been developed that can theoretically modulate expression of any given gene, the emergence of reliable reporter assays greatly facilitates the search for transcription-targeted agents. This review provides a comprehensive overview of these developments, and discusses various strategies applicable for developing transcription-targeted therapeutic agents.
KW - Cancer
KW - Drug development
KW - Targeted therapy
KW - Transcription
KW - Transcription therapy
KW - Transcriptional regulation
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U2 - 10.1016/j.bbcan.2012.11.002
DO - 10.1016/j.bbcan.2012.11.002
M3 - Review article
C2 - 23147197
AN - SCOPUS:84869861385
SN - 0304-419X
VL - 1835
SP - 76
EP - 85
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
IS - 1
ER -